The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males.
Autophagy
; 18(7): 1662-1672, 2022 07.
Article
in English
| MEDLINE | ID: covidwho-1585354
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(IC). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways.Abbreviations AP autophagosome; AUC area under the curve; BafA1 bafilomycin A1; COVID-19 coronavirus disease-2019; HCQ hydroxychloroquine; RAP rapamycin; ROC receiver operating characteristic; SARS-CoV-2 severe acute respiratory syndrome coronavirus 2; TLR toll like receptor; TNF/TNF-α tumor necrosis factor.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Toll-Like Receptor 3
/
COVID-19
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Limits:
Humans
/
Male
Language:
English
Journal:
Autophagy
Year:
2022
Document Type:
Article
Affiliation country:
15548627.2021.1995152
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